Familial Chiari Type 1: A Molecular Karyotyping Study in a Turkish Family and Review of the Literature

Background The etiology of Chiari I malformation (CMI) has not been fully elucidated. Therefore, we performed a genetic study of a Turkish family in which 3 sisters had a diagnosis of CMI with or without syringomyelia. Methods In a family with 7 children, 4 daughters complained of occipital headaches. In 2 of these daughters, CMI had been diagnosed during their 30s, and CMI plus syrinx had been diagnosed in the other daughter in her 40s. Cranial magnetic resonance imaging of the fourth daughter who had developed headaches during her 30s showed normal findings. Because the other siblings in the family were asymptomatic, radiological examinations were not performed. The family had a history of distant consanguineous marriage between parents. Additionally, the father had died, and the mother was asymptomatic, with radiologically normal findings. Array comparative genome hybridization studies were performed for 12 persons from 3 generations of this family. Results None of the 12 cases examined harbored copy number variations. Conclusions This family with 3 sisters having CMI suggested a possible autosomal recessive single-gene etiology. Cases of familial CMI are unusual but important to study because they could reveal the specific genes involved in posterior fossa/foramen magnum structure and function and provide insights into the cause of sporadic cases.